Angiotensin II (Ang II) is the principal mediator of the physiological effects of the renin-angiotensin system (RAS). All of the components of the RAS are present in the heart. Studies demonstrate that growth of cultured cardiac cells following static stretch (an in vitro model of cardiac hypertrophy) is blocked by an Ang II receptor antagonist, providing the most compelling evidence to date that locally-produced Ang II plays a role in cardiac growth. In addition, changes in the expression of components of the RAS following pressure-overload (an in vivo model of cardiac Hypertrophy) suggest that this humoral system is involved in pathophysiological growth of the heart. The overall goal of this proposal is to test the hypothesis that the cardiac ARS contributes to growth of cardiac cells in vitro and in vivo. I AIM I, we will determine the expression of components of the RAS in cultured cardiac myocytes and fibroblasts following static stretch using multiplex reverse transcription-polymerase chain reaction titration assay (MPTA) (for mRNAs) and Western blot analysis (for proteins). In AIM II, we will determine the expression of cardiac RAS components following left ventricular pressure-overload. Cardiac cells that express components of the RAS will be identifies using in situ hybridization and immunohistochemistry. Finally, in vitro and in vivo gene transfer will be used to test the hypothesis that locally-produced Ang II plays a role in cardiac growth.